A case of mucocutaneous leishmaniasis diagnosed by serology.

A 43-year-old Japanese Bolivian male had been suffering from a right leg ulcer after an insect bite during his residence in Bolivia. The ulcer healed after herbal medicine treatment. Ten years later, the patient had symptoms of nasal obstruction, nasal bleeding, and pharyngodynia, which were accompanied by a destructive ulcer with surrounding erythema involving the right nostril apex and columella. Papillary, irregular mucosal lesions were seen on the soft palate. Giemsa staining and polymerase chain reaction (PCR) using biopsy specimens of the papillary mucosal lesions on the soft palate failed to identify Leishmania parasites. However, the IgG antibody test was positive for Leishmania (Leishmania) donovani, and the dot enzyme-linked immunosorbent assay (dot-ELISA) using five Leishmania antigens L. (L.) mexicana, L. (L.) amazonensis, Leishmania (Viannia) guyanensis, L. (V.) braziliensis, and L. (V.) panamensis was positive. Combined, the findings suggested mucocutaneous leishmaniasis. Treatment with liposomal amphotericin B was started but was soon terminated because of palpitation, epigastralgia and facial flushing. It is sometimes difficult to identify the parasites in lesions of mucocutaneous leishmaniasis and serological tests are useful for such occasions.

Fixed eruption due to quinine in tonic water: a case report with high-performance liquid chromatography and ultraviolet A analyses.

Fixed drug eruption is a common cutaneous adverse reaction in young patients with a characteristic clinical appearance. However, the diagnosis and identification of the substance may be difficult if food or food additives provoke the fixed eruption. A 26-year-old man had a history of two episodes of cutaneous erythema with residual pigmentation. Close examination of the history including his diet in addition to an oral challenge test and patch testing led to the diagnosis of fixed eruption secondary to quinine in tonic water. We examined for the presence of quinine in commercially available brands of tonic water using ultraviolet A and irradiation and high-performance liquid chromatography. Both Schweppes and CANADA DRY brands of tonic water emitted fluorescent light upon ultraviolet A irradiation, and contained quinine at concentrations of 67.9 and 61.3 mg/L, respectively. Quinine contained in some tonic waters may trigger fixed eruption.

Deep venous thrombosis and pulmonary embolism secondary to co-administration of thalidomide and oral corticosteroid in a patient with leprosy.

A 58-year-old Japanese man with a 2-year history of multidrug therapy for borderline lepromatous leprosy presented with skin lesions suggestive of erythema nodosum leprosum (ENL) and was treated with an oral corticosteroid. As attempts to taper the oral corticosteroid resulted in the appearance of new lesions, thalidomide was added along with cyclosporin. Two months after the introduction of thalidomide, deep venous thrombosis (DVT) occurred in both legs and anticoagulant therapy was started without cessation of thalidomide. Pulmonary embolism developed 1 month after the appearance of DVT, and these thromboembolic events were believed to be due to thalidomide. This case highlights the need for vigilance against venous thromboembolism when corticosteroid and thalidomide are co-administrated for the treatment of ENL.

Systemic lupus erythematosus complicated with protein-losing enteropathy: a case report and review of the published works.

A 45-year-old man was referred to our hospital with a history of multiple erythematous skin lesions of several months' duration. Blood examination revealed extreme hypoproteinemia and hypoalbuminemia, as well as the presence of antinuclear antibodies. A skin biopsy specimen showed liquefaction degeneration at the dermoepidermal junction and dense lymphocyte and neutrophil infiltration around the vessels and appendages in the upper and middle dermis. Chest X-ray and computed tomography showed a pleural effusion and thoracic paracentesis revealed a mononuclear cell-dominant cell infiltration, suggestive of serositis. Technetium-99m ((99m)Tc)-labeled human serum albumin scintigraphy and α(1)-antitrypsin clearance revealed protein leakage along the digestive tracts from the stomach to the jejunum. From the above findings, the patient was diagnosed with systemic lupus erythematosus (SLE) complicated by protein-losing enteropathy (PLE). Treatment with oral prednisolone significantly improved his clinical symptoms and hypoalbuminemia. This case highlighted the utility of (99m)Tc-labeled human serum albumin scintigraphy and α(1)-antitrypsin clearance in the diagnosis of PLE. We also present a published work review on PLE associated with connective tissue disease revealing a relatively higher prevalence in patients of Asian ethnicity, including Japanese.

Allergic contact dermatitis due to diclofenac sodium in eye drops.

Eyelid dermatitis and/or periocular dermatitis (ED/PD) is commonly seen in a variety of skin diseases such as seborrheic dermatitis, atopic dermatitis and psoriasis, but is most often associated with allergic contact dermatitis (ACD). Here, a case of ACD in an 82-year-old man is described; he used 0.1% diclofenac sodium eye drops and exhibited pruritic erythema on the eyelids. Patch test for diclofenac sodium eye drops was positive. Further patch tests revealed a positive reaction to diclofenac sodium (monosodium 2-[2, 6-dichlorophenylamino] phenylacetate), which was the main component in the eye drop medicine. Diclofenac sodium is a non-steroidal anti-inflammatory drug (NSAID), and is frequently used in everyday oral medications, topical ointments, gel agents and eye drops. Case reports on ACD caused by diclofenac sodium eye drops are extremely rare. Nevertheless, it is necessary to consider ACD due to diclofenac sodium when a patient with ED/PD has a history of use of diclofenac sodium eye drops.

Phaeohyphomycosis caused by Exophiala jeanselmei in a patient with polymyalgia rheumatica.

An 87-year-old man, a gardener in Okinawa, first noticed a tumor on the dorsum of his right hand in November 2005. He had been taking prednisolone for the treatment of polymyalgia rheumatica since 2000. A nearby dermatologist incised the tumor for pus drainage in February 2006. In April of the same year, the dome-like tumor reappeared. The same treatment was repeated. Because the culture of the pus revealed fungi at that time, terbinafine hydrochloride and minocycline were administrated under the diagnosis of a deep fungal infection. After a short remission, the tumor recurred in November of the same year and in May and August of 2007 regardless of the repeated incision and pus drainage. He was referred to our hospital on 27 September 2007. His first physical examination at our outpatient office showed a skin-colored, well-demarcated, multilocular, cystic subcutaneous tumor on the dorsum of his right hand. Histopathological examination revealed a pseudocyst with fibrous walls of connective tissue. Continuous, bead-like hyphae, positive with periodic acid-Schiff stain and Grocott stain, were found within the pseudocyst. Morphological and molecular biological examinations of the separately cultured specimens identified the causative agent as Exophiala jeanselmei. The entire cyst was removed under local anesthesia, and an artificial dermis made of silicon membrane was applied to the wound. Skin graft was performed in November after confirming no recurrence of the fungal infection. Terbinafine hydrochloride 125 mg/day has continued. No recurrence has been observed up to now.

Necrotizing fasciitis caused by Streptococcus pneumoniae.

A 69-year-old woman presented with shivering and pain in the lower extremities on 5 April 2006; she was referred to the dermatology division of our hospital on the following day with difficulty in walking. She had been suffering from non-viral, non-alcoholic liver cirrhosis, and was being treated by the Division of Internal Medicine. Physical examination showed edema in the lower extremities and light purpuras on the groin and legs. Low blood pressure had been observed since admission. Necrotizing fasciitis (NF) was suspected on the basis of the skin symptoms, systemic conditions, and magnetic resonance imaging. During surgical debridement under general anesthesia, cardiopulmonary arrest occurred, and the patient died 12 h after admission. NF, in its early stages, exhibits few skin changes. In order to differentiate it from other skin infections, it is necessary to take into account blood pressure, abnormal systemic conditions, and severe pain out of proportion to its minor skin changes. In the present case, Streptococcus pneumoniae was detected by blood culture. Soft tissue infectious diseases caused by S. pneumoniae, especially NF, are very rare. We have reviewed reported cases of NF caused by S. pneumoniae.

Neonatal pemphigus vulgaris.

A male newborn with skin erosions was born to a 32-year-old woman who was under treatment for pemphigus vulgaris that had been diagnosed 16 months earlier. Antibodies to desmoglein (Dsg)1 and Dsg3 were analyzed by enzyme-linked immunosorbent assay. Index values of antibodies to Dsg1 and Dsg3 were 49 (normal index values, <14) and 121 (normal index values, <7), respectively. Those findings concluded a diagnosis of neonatal pemphigus vulgaris. No new vesicles or bullae appeared in the newborn after the birth. Non-corticosteroid ointments produced prompt epithelialization on the erosive lesions. All the eruptions disappeared in 3 weeks. The level of serum anti-Dsg3 autoantibodies when measured at the 76th day was negative (<5).

Case of linear immunoglobulin A bullous dermatosis associated with acquired hemophilia.

Linear immunoglobulin (Ig)A bullous dermatosis is a rare autoimmune subepidermal bullous dermatosis caused by circulating IgA autoantibodies directed against the antigens at the basement membrane zone. Most linear IgA bullous dermatosis cases are idiopathic, but some are associated with the use of certain drugs, infections, lymphoproliferative disorders, internal malignancies, autoimmune disorders, collagen diseases or, very rarely, other skin diseases, including autoimmune bullous diseases. Acquired hemophilia is also rare; it is a coagulation disease caused by anti-factor VIII IgG antibodies. Acquired hemophilia has been reported to be associated with malignant tumors, pregnancy or postpartum, drug reactions, collagen diseases such as rheumatoid arthritis, autoimmune disorders, and skin diseases such as psoriasis and pemphigus. We report a case of hemophilia acquired during the course of linear IgA bullous dermatosis and review reported cases of autoimmune bullous dermatoses associated with acquired hemophilia.

Case of chromoblastomycosis appearing in an Okinawa patient with a medical history of Hansen's disease.

Chromoblastomycosis is one of several chronic infectious skin diseases caused by various species of dematiaceous fungi. It is clinically characterized by verrucous skin eruptions and occurs most commonly in tropical and subtropical regions. In Okinawa, a subtropical area, there have been only three reported cases of chromoblastomycosis including the present one. Direct microscopic examination of crust specimens and findings of sclerotic cells in histopathology can confirm the diagnosis, and cultures of crust and/or tissue specimens can identify the causative fungi. We herein report the third case of chromoblastomycosis in Okinawa; it arose in an 87-year-old Japanese woman with a history of Hansen's disease, who lived in a leprosarium in Miyako Island. To identify the causative agent as Fonsecaea pedrosoi, we used the polymerase chain reaction and direct sequencing analysis in addition to the usual methods, which include 20% potassium hydroxide microscopy, histopathological confirmation of sclerotic cells by periodic acid-Schiff stain, culture by Sabouraud's glucose agar, slide culture method, and observation of conidia by scanning electron microscopic examination.

Case of skin injuries due to stings by crown-of-thorns starfish (Acanthaster planci).

A case of skin injuries due to stings by crown-of-thorns starfish, Acanthaster planci, in a 53-year-old Okinawan woman is reported. She went to a beach to gather shellfish on 8 April 2001 and fell to the ground with her left palm on a crown-of-thorns starfish that happened to be close to her. She hurried to the emergency section of our hospital. An emergency doctor sterilized the wound and administered an antibiotic, an analgesic agent and an injection of a tetanus antitoxin. He tried to remove the remaining spines from the palm with great difficulty. Because swelling and subcutaneous indurations of the left palm had persisted thereafter, oral and topical administration of corticosteroid started on 13 April. Physical examination at the dermatology section revealed approximately 10 stab wounds of the left palm with pus, subcutaneous bleeding and many abrasions around them. X-rays of the left hand showed foreign bodies, 2-10 mm in size, located on the lesions. The patient was treated with a topical injection of 2 mg triamcinolone acetonide (Kenacort-A), diluted fivefold with 1% Xylocaine, once a week. Some of the foreign body granulomatous lesions improved but pain and subcutaneous indurations persisted in most of the lesions. Because the X-ray photographs showed many remaining spines, surgical excision to remove them was performed under local anesthesia 3 months after the injury. All the symptoms improved after the operation. Scanning electron microscopic examination of the spines revealed that their tips had fragile lattice-like structures.

Case of pemphigus foliaceus that shifted into pemphigus vulgaris after adrenal tumor resection.

A 79-year-old Japanese woman visited our hospital on 6 May 2003, who had suffered from erythema and crusted vesicles located on the head, face and trunk. The eruptions first appeared in February 2003. Histopathological findings included blister formation spreading from just below the horny layers to the upper squamous layers, where acantholytic cells were observed. Direct immunofluorescence disclosed immunoglobulin G depositions in the epidermal intercellular spaces. Enzyme-linked immunosorbent assay showed an elevated titer of anti-desmoglein (Dsg)1 autoantibodies (154 index value), but almost normal levels of anti-Dsg3 autoantibodies (8 index value in serum). The diagnosis at first was made as pemphigus foliaceus (PF). Topical use of corticosteroids alone could control the eruptions well. Systemic examinations on admission revealed a right adrenal tumor that had caused Cushing's syndrome. Its resection was performed on 24 July 2003. Histopathological diagnosis of the removed tumor was a functional adrenal adenoma. The symptoms had worsened after the resection. Topical use of corticosteroids alone could no longer control the symptoms. Additional p.o. medications of minocycline hydrochloride and nicotinic acid amides improved the symptoms to some extent. However, oral cavity erosions appeared in December 2004, and the titer of anti-Dsg3 autoantibodies in serum elevated, suggesting a transition from PF to pemphigus vulgaris (PV). p.o. administration of corticosteroids started, which improved the symptoms significantly. To date, there have been no reports of pemphigus complicated with an adrenal tumor that caused Cushing's syndrome in Japan. The present case is particularly interesting in that the symptoms became worse after the tumor resection and that the first diagnosis of PF shifted into PV after the operation.

IL-18 gene polymorphisms affect IL-18 production capability by monocytes.

We previously demonstrated a significant association between IL-18 gene polymorphism 105A/C and asthma. In this study, we investigated the relationship of IL-18 gene polymorphism to IL-18 production capability by monocytes. The frequency of gene polymorphisms including IL-18-105A/C and IL-18--137G/C was determined by PCR analyses. The IL-18 production by monocytes stimulated without or with LPS or A23187+PMA for 1day was measured by ELISA. The produced IL-18 spontaneously or in response to A23187+PMA by monocytes was significantly higher for volunteers with 105A/A genotype than with 105A/C genotype. Similarly, the production capability of IL-18 by monocytes from volunteers with -137G/G genotype was significantly higher than that with -137G/C genotype and significant linkage disequilibrium was observed between 105A/C and -137G/C polymorphism. Thus, the genetic capacity to produce more IL-18 in response to stimuli may affect the onset of asthma.

A case of tinea nigra palmaris in Okinawa, Japan.

We report a case of tinea nigra on the left palm of a 13-year-old girl. She had noticed a pigmented, asymptomatic macule on the left palm approximately 4-5 years prior to her first visit to our hospital. The color of the lesion tended to change before and after a bath; it became lighter after a bath and darkened some time later. Physical examination revealed that the macule was 4 cm x 5 cm in size, dark brown in color and irregularly shaped. Direct potassium hydroxide (KOH) microscopic examination from skin scrapings revealed branched brown hyphae with light brown septa. A fungal culture on Sabouraud's agar media produced wet, medium brown, yeast-like colonies, the surface of which later became black and shiny. A slide culture disclosed light brown, elliptic or peanut-shaped conidia comprised of one to two ampullaceous cells. Scanning electron microscopic examination of the conidia showed both annellation conidia with lunate bud scars and sympodial conidiogenesis. Using extracted DNA from separately cultured fungi, we performed polymerase chain reaction with the primers specific to Hortaea werneckii. The results showed positive bands. We performed direct sequencing with the DNA segments from the positive bands. The causative fungus in our case was determined to be type C of H. werneckii on the grounds of the base sequences obtained. The final diagnosis of the present case was made as tinea nigra by H. werneckii. We also report a brief survey of all the cases of tinea nigra reported in Japan to date.

The attachment and entry of Leishmania (Leishmania) major into macrophages: observation by scanning electron microscope.

Leishmaniasis, a zoonotic protozoan disease, starts with the inoculation of the Leishmania promastigotes into the skin at the time of blood ingestion by a female sandfly. The infection of leishmaniasis is established when the Leishmania organisms start their own intracellular multiplication after having been phagocytized by the host's macrophages. In the earliest stage of the infection, therefore, the attachment of the promastigates to the macrophages is essential. We incubated a mixed culture of macrophages (JM774-1A) and Leishmania (Leishmania) major for 6 hours in vitro and observed the process of the attachment between the parasite and host cell by scanning electron microscope. We found for the first time that the attachment between the two occurred at the site of the parasite body, in addition to the previously reported sites of the flagellar tip, flagellar base, and aflagellar tip (posterior pole).

A genotype distribution of human papillomaviruses detected by polymerase chain reaction and direct sequencing analysis in a large sample of common warts in Japan.

There have been no large-scale epidemiological studies of human papillomavirus (HPV) genotype distribution of common warts in Japan. A total of 213 patients with common warts (104 males and 109 females) in Japan were studied to detect HPV genotype distribution by polymerase chain reaction (PCR) and direct sequencing analysis. The results were as follows: 94 HPV-1a (44.1%), 35 HPV-4 (16.4%), 30 HPV-65 (14.1%), 13 HPV-27 (6.1%), 13 HPV-2a (6.1%), 9 HPV-57b (4.22%), 3 HPV-16 (1.41%), 2 HPV-6a (0.94%), 2 HPV-63 (0.94%), and 1 case for each of HPV-3, -5, -5b, -7, -10, -21, -29, -47, -56, -57, -62, and -92 (0.47%, respectively). Four cases (1.88%) were found in which two different HPV types were detected within the lesions: one case of HPV-1a with HPV-16, one case of HPV-1a with HPV-65, one case of HPV-6a with HPV-8, and one case of HPV-65 with HPV-16. There were seven cases of mucosal types (3.3%), that is, two HPV-6a, three HPV-16, one HPV-56, and one HPV-62, and three cases of epidermodysplasia verruciformis (EV)-related types (1.41%), that is, one HPV-5, one HPV-5b (both of which belonged to a high-risk group), and one HPV-47 (which belonged to a low-risk group). To date, this is the largest sequencing-based study of HPV for common warts in Japan. It is said that common warts are induced predominantly by HPV-2, -27, and -57 in European population. However, the present results showed that in Japan they were induced mostly by HPV-1, -4, and -65. This suggests that regional differences in HPV genotype distribution may exist between European and Japanese populations.

PTHrP-producing tumor: squamous cell carcinoma of the liver accompanied by humoral hypercalcemia of malignancy, increased IL-6 and leukocytosis.

A 77-year-old man was admitted to our hospital showing symptoms of general fatigue and appetite loss. He had leukocytosis, thrombocytosis and hypercalcemia with elevated serum levels of parathyroid hormone related peptide (PTHrP) and interleukin-6 (IL-6). An increase in tumor markers SCC and CYFURA21-1 was observed. The liver contained a huge tumor, which was proved to be PTHrP producing squamous cell carcinoma by immuno-histochemical analysis. Since the tumor did not express IL-6, it was assumed to be induced by PTHrP in osteoblasts. This is the first report of PTHrP producing squamous cell carcinoma of the liver.

Un estudio ultraestructural de leishmaniasis cutáneo difusa causada por Leishmania (Leishmania) mexicana en Ecuador: el rol de la vacuola parasitófora en la interacción macrófago-parásito

En el presente estudio se realizó una observación con microscopía electrónica de materiales de biopsias de piel de un paciente con leishmaniasis cutánea difusa (LCD), y otro con leishmaniasis cutánea localizada (LCL) en Ecuador. Se observaron grandes vacuolas parasitóforas (VPs) y membranas celulares desconectadas de asmtigotes de Leishmania, solamente en LCD. El márgen de la membrana celular en el sitio de desconexión estaba doblado hacia fuera. Estos hallazgos sugieren que fosfoglico-proteínas de alto peso molecular se liberan en el sitio desconectado de las membranas de loas amastigotes, y que este fenómeno fue más acelrado en la LCD que en la LCL.

Leishmaniasis cutáneo difusa: diferencia patológica entre formas localizada y difusa

Un caso de leishmaniasis cutáneo difusa (LCD) y 2 casos de leishmaniasis cutánea localizada (LCL) fueron examinados inmunohistoquímicamente utilizando un anticuerpo CD45RO anti-células T, y anticuerpos antilysozyme. Los linfocitos-T se infiltraron a través de la dermis y fueron observados rodeando los macrófagos en las lesiones de LCL. En contraste con esto, los macrófagos en las lesiones de LCD no se activaron como aquellos de la LCL. Se deduce que los macrófagos no pueden desarrollar su papel como células presentadores de antígeno en las lesiones de LCD.